Effect of a single dose of 8 mg moxidectin or 150 µg/kg ivermectin on O. volvulus skin microfilariae in a randomized trial: Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection

Abstract

AbstractBackgroundCommunity-directed treatment with 150 µg/kg ivermectin (CDTI), the current control strategy, is insufficient for eliminating Onchocerca volvulus transmission across sub-Saharan Africa. Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo (DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150µg/kg ivermectin dose.Methodology/Principal FindingsWe analysed drug efficacy by study area and pre-treatment SmfD (intensity of infection, IoI). Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10-20, ≥20-<50, ≥50-<80, ≥80, respectively. Ivermectin’s efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p≤0.002) and moxidectin’s efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p<0.006). Odds ratios for UD1-6, UD1-12 or UD1-18 after moxidectin versus ivermectin treatment exceeded 7.0. Suboptimal response (SmfD 12 months post-treatment >40% of pre-treatment SmfD) occurred in 0%, 0.3%, 1.6% and 3.9% of moxidectin and 12.1%, 23.7%, 10.8% and 28.0% of ivermectin treated participants in Nord Kivu, Ituri, Lofa and Nkwanta, respectively.Conclusions/significanceThe benefit of moxidectin vs ivermectin treatment increased with pre-treatment IoI. The possibility that parasite populations in different areas have different drug susceptibility without prior ivermectin selection pressure needs to be considered and further investigated.Author SummaryOnchocerciasis or river blindness is a parasitic disease primarily in sub-Saharan Africa and Yemen. It can cause debilitating morbidity including severe itching, skin changes, visual impairment and even blindness. Many years of control efforts, today primarily based on mass administration of ivermectin (MDA) in endemic communities, have reduced morbidity and the percentage of infected individuals so that elimination of parasite transmission is now planned. WHO estimated that in 2020 more than 239 million people required MDA. Ivermectin may not be sufficiently efficacious to achieve elimination everywhere. Our study in areas in Liberia, Ghana and the Democratic Republic of the Congo where MDA had not been implemented yet showed that moxidectin reduced parasite levels in the skin better and for longer than ivermectin. Here we show that people with higher numbers of parasites in the skin benefit more from moxidectin treatment than those with lower numbers and that the efficacy of ivermectin and moxidectin differs between study areas. Provided WHO and countries include moxidectin in guidelines and policies, this information could help decisions on when and where to use moxidectin.